A New Molecule for Memory: It can Enhance, or Erase

Taking the memory-erasing ability shown in the 2004 movie "Eternal Sunshine of the Spotless Mind" a step further, scientists have found a molecule that not only erases but also augments and strengthens memories, months after the fact.

"If you take coffee or amphetamines that make the brain more excitable, your initial learning can be a little better, as any student would know," said researcher Todd Sacktor of SUNY Downstate Medical Center. "What never had been done before was to be able to, after you learn something, wait days to weeks later, and then do something that would be able to enhance those previously stored memories."

Previous studies of memory-modulating compounds have mainly been focused on treatment during periods of learning or remembering. Sacktor's research has pinpointed a brain enzyme that plays an integral role in the maintenance of long-term memory.

Where memories are made

Sacktor and co-researcher Yadin Dudai of the Weizmann Institute of Science in Israel conditioned rats to associate a taste with feeling sick to their stomachs, much like humans after a particularly nasty batch of food poisoning. This memory becomes encoded in the brain and for months after the nauseating experience the rats avoid any similar-tasting foods.

To change the rats' memories the researchers first trained them to associate certain foods with bellyaches, then injected them with a non-illness-inducing virus made specifically to express a memory-altering enzyme. The enzyme is called protein kinase M zeta, or PKMzeta for short. The virus made either the working version of the protein or a mutant form that blocked the activity of even the naturally expressed protein.

The memory molecule, PKMzeta (red color) in rat brain cells (green). Rats with more PKMzeta in their brain come to have a stronger long-term memory. The variegated yellow (right panel) is the is the mixture of the two stains, showing that PMKzeta is expressed in the brain cell, but in some contact points and not others.

Credit: Weizmann Institute of Science, Rehovot, Israel

They saw that the increased enzyme levels enhanced the rat's ability to remember, while the activity-blocking mutant wiped out the memory.

PKMzeta appears to work in a different way than other memory enhancers, which seem to boost our brain's natural means of consolidating, or turning everyday experiences into lasting memories. But scientists didn't know the mechanism that keeps these long-term memories accessible after consolidation.

Dudai and his team believe that PKMzeta is integral in this "sustainability" of memories. "People used to think that memory maintenance is a passive process, that there wasn't much to put into it, that you just change the wiring," Karim Nader, a researcher at McGill University in Canada who wasn't involved in the study, said. "This suggests that the mechanisms of memory maintenance are actively maintained, and even manipulated."

Next memory-boosting drug?

In the future, it's possible this protein could be the target of memory-changing drugs. Such drugs could treat Alzheimer's patients, by strengthening their memories, or individuals with post-traumatic stress disorder (PTSD) as well as phobia patients, by decreasing their memory of fear-inducing moments. Different memories could be targeted by changing PKMzeta in different brain areas.

"There are other molecules that have been implicated in memory maintenance," David Glanzman of UCLA, who wasn't involved in the study, told LiveScience. "But it's clear that PKMzeta is a sort of master molecule."

Even after having their memory of the nauseating taste wiped out, the rats could still relearn to dislike it, similar to (spoiler alert!) the reunion of the “Spotless Mind” characters after their first memory wipe. "That area of the brain is still capable of learning new things," Dudai said."We didn't damage it to such a degree that we interfered with this ability."

This study will be published in the March 4 issue of the journal Science.

Jennifer Welsh graduated from the University of California, Santa Cruz's Science Communication graduate program after working at a start up biotech company for three years after getting her Bachelor of Science in Biological Sciences from the University of Notre Dame. She has worked at WiredScience, The Scientist and Discover Magazine before joining the Live Science team.